{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T19:25:15Z","timestamp":1771529115095,"version":"3.50.1"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Populations of cultured mouse embryonic stem cells (ESCs) exhibit a subfraction of cells expressing uncharacteristically low levels of pluripotency markers such as Nanog. Yet, the extent to which individual Nanog-negative cells are differentiated, both from ESCs and from each other, remains unclear. Here, we show the transcriptome of Nanog-negative cells exhibits expression of classes of genes associated with differentiation that are not yet active in cells exposed to differentiation conditions for one day. Long non-coding RNAs, however, exhibit more changes in expression in the one-day-differentiated cells than in Nanog-negative cells. These results are consistent with the concept that Nanog-negative cells may contain subpopulations of both lineage-primed and differentiated cells. Single cell analysis showed that Nanog-negative cells display substantial and coherent heterogeneity in lineage marker expression in progressively nested subsets of cells exhibiting low levels of <jats:italic>Nanog<\/jats:italic>, then low levels of <jats:italic>Oct4<\/jats:italic> and then a set of lineage markers, which express intensely in a small subset of these more differentiated cells. Our results suggest that the observed enrichment of lineage-specific marker gene expression in Nanog-negative cells is associated with spontaneous differentiation of a subset of these cells rather than the more random expression that may be associated with reversible lineage priming.<\/jats:p>","DOI":"10.1038\/srep13339","type":"journal-article","created":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T09:46:08Z","timestamp":1440150368000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Heterogeneous lineage marker expression in naive embryonic stem cells is mostly due to spontaneous differentiation"],"prefix":"10.1038","volume":"5","author":[{"given":"Gautham","family":"Nair","sequence":"first","affiliation":[]},{"given":"Elsa","family":"Abranches","sequence":"additional","affiliation":[]},{"given":"Ana M. 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A.R. has consulted for Biosearch Technologies and has received royalty income from intellectual property related to RNA FISH licensed to Biosearch Technologies. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"13339"}}